Rates of noninsulin-mediated glucose uptake are elevated in Type II diabetic subjects

A. D. Baron, O. G. Kolterman, J. Bell, L. J. Mandarino, J. M. Olefsky

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Abstract

Although insulin is extremely potent in regulating glucose transport in insulin-sensitive tissues, all tissues are capable of taking up glucose by facilitated diffusion by means of a noninsulin-mediated glucose uptake (NIMGU) system. Several reports have estimated that in the postabsorptive state the majority of glucose disposal occurs via a NIMGU mechanism. However, these estimates have been either derived or extrapolated in normal humans. In the present study we have directly measured NIMGU rates in 11 normal (C) and 7 Type II noninsulin-dependent diabetic subjects (NIDDM; mean±SE fasting serum glucose, 249±24 mg/dl). To accomplish this, the serum glucose was clamped at a desired level during a period of insulin deficiency induced by a somatostatin infusion (SRIF, 550 μg/h). With a concomitant [3-3H]glucose infusion, we could isotopically quantitate glucose disposal rates (R(d)) during basal (basal insulin present) and insulin-deficient (SRIF) conditions. With this approach we found that (a) basal R(d) was greater in NIDDM than in C, 274±31 vs. 150±7 mg/min, due to elevated hepatic glucose output, (b) NIMGU composes 75±5% of basal R(d) in C and 71±4% in NIDDM, (c) NIDDMS have absolute basal NIMGU rates that are twice that of C (195±23 vs. 113±8 mg/min, P < 0.05), (d) when C were studied under conditions of insulin deficiency (SRIF infusion) and at a serum glucose level comparable to that of the NIDDM group (250 mg/dl), their rates of NIMGU were the same as that of the NIDDM group (186±19 vs. 195±23 mg/min; NS). We conclude that (a) in the postabsorptive state, NIMGU is the major pathway for glucose disposal for both C and NIDDM; (b) for a given glucose level the efficiency of NIMGU (NIMGU divided by serum glucose level) is equal in C and NIDDM, but since basal R(d) is elevated in NIDDMs their absolute basal rates of NIMGU are higher; and (c) elevated basal rates of NIMGU in NIDDM may play a role in the pathogenesis of the late complications of diabetes.

Original languageEnglish (US)
Pages (from-to)1782-1788
Number of pages7
JournalJournal of Clinical Investigation
Volume76
Issue number5
Publication statusPublished - 1985
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

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Baron, A. D., Kolterman, O. G., Bell, J., Mandarino, L. J., & Olefsky, J. M. (1985). Rates of noninsulin-mediated glucose uptake are elevated in Type II diabetic subjects. Journal of Clinical Investigation, 76(5), 1782-1788.